Tiziana Reports Phase 2a Clinical Data with Milciclib Monotherapy in Sorafenib-refractory or -intolerant patients with unresectable or metastatic Hepatocellular Carcinoma.
· Milciclib was well tolerated and no drug-related deaths were reported
· 28 out of 31 treated patients were evaluable, with 14 patients completing the 6-month study duration
· 9 patients continued treatment under compassionate use, of which 5 are currently continuing with treatment
New York/London, 22 July 2019 – Tiziana Life Sciences plc (NASDAQ: TLSA / AIM: TILS), a biotechnology company focusing on the discovery and development of innovative therapeutics for inflammation and oncology indications, today announced preliminary topline clinical data from a Phase 2a trial of Milciclib as a monotherapy in patients with advanced hepatocellular carcinoma (HCC), the most common form of liver cancer. The primary endpoint of the study was overall safety. Under compassionate use, a few patients continued with total treatment for up to 16 months. Overall, treatment with Milciclib was well-tolerated and no drug-related deaths were recorded. Secondary endpoints of efficacy including progression-free survival (PFS) and time to progression (TTP) are currently being evaluated and will subsequently be reported.
This Phase 2a trial with Milciclib monotherapy was a multi-centre, single-arm, repeated-dose (100 mg once daily; 4 days on/3 days off every 4 weeks; defining each cycle), 6-month duration study to evaluate the safety, tolerability and anti-tumour activity of Milciclib in sorafenib-refractory or intolerant patients with unresectable or metastatic advanced HCC. This trial enrolled 31 patients in Italy, Greece, and Israel.
Among the 28 evaluable patients, 14 completed the 6-month duration study. Oral treatment with Milciclib was well-tolerated with manageable toxicities. The most frequent adverse events such as diarrhoea, ascites, nausea, fatigue, asthenia, fever, ataxia, headache, and rash were manageable.
9 out of the 14 patients, after completing the 6-month trial period, requested to continue the treatment under compassionate use and were approved by their respective ethical committees. Four of the patients received Milciclib for a total of 9, 11, 13 and 16 months. The remaining 5 patients are continuing treatment with Milciclib are at 8th, 9th, 9th, 9th and 11th month currently.
Objective tumour assessments according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) guideline and the conventional RECIST 1.1 criteria are being conducted by Independent Central Review and data will be available on September 2019.
“We are very pleased with the clinical activity and tolerability of Milciclib in these advanced cases of HCC. It is an important milestone to move forward with the further clinical development of Milciclib either as a single agent or in combination with other HCC drugs,” said Dr Kunwar Shailubhai, CEO & CSO of Tiziana.
These data are consistent with the earlier reported long-term safety and clinical activity of Milciclib in thymic carcinoma, thymoma1 and other solid cancers2.
The global market for liver cancer drugs is estimated to reach $1.47 billion by 2022. The current standard of care drugs is not entirely satisfactory due to low response rates and severe toxicities. Importantly, patients often become resistant or unresponsive to the treatment. Milciclib works through a unique mechanism of action and the Company, therefore, believes it may have the potential for long-term efficacy with a good safety profile in a larger subset of patients.
The person who arranged for the release of this announcement on behalf of the Company was Dr Kunwar Shailubhai, CEO & CSO of Tiziana.
1. Besse, B., Garassino, M., Rajan, A., Novello, S., Mazieres, J., Weiss, G., Kocs, D., Barnett, J, Davite, C, Crivori, P and G. Giaccone. Efficacy of milcicilib (PHA-848125AC), a pan-cyclin D -dependent kinase inhibitor in tow phase II studies with Thymic carcinoma and B3 thymoma patients. (2018) J. Clin. Onc 36 (15 suppl): 8519
2. Aspeslagh, S., Shailubhai, K., Bahleda, R. et al. (2017). Phase I dose-escalation study of Milciclib in combination with gemcitabine in patients with refractory solid tumours. Cancer Chemother Pharmacol. 79:1257-1265.